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The mPer2 gene encodes a functional component of the mammalian circadian clock

Author

Listed:
  • Binhai Zheng

    (Department of Molecular and Human Genetics)

  • David W. Larkin

    (Division of Neuroscience)

  • Urs Albrecht

    (Verna and Marrs McLean Department of Biochemistry
    Max Planck Institute for Experimental Endocrinology)

  • Zhong Sheng Sun

    (Department of Molecular and Human Genetics)

  • Marijke Sage

    (Department of Molecular and Human Genetics)

  • Gregor Eichele

    (Verna and Marrs McLean Department of Biochemistry
    Max Planck Institute for Experimental Endocrinology)

  • Cheng Chi Lee

    (Department of Molecular and Human Genetics)

  • Allan Bradley

    (Department of Molecular and Human Genetics
    Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza)

Abstract

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms1. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified2,3,4,5,6,7,8. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.

Suggested Citation

  • Binhai Zheng & David W. Larkin & Urs Albrecht & Zhong Sheng Sun & Marijke Sage & Gregor Eichele & Cheng Chi Lee & Allan Bradley, 1999. "The mPer2 gene encodes a functional component of the mammalian circadian clock," Nature, Nature, vol. 400(6740), pages 169-173, July.
    • Handle: RePEc:nat:nature:v:400:y:1999:i:6740:d:10.1038_22118
    DOI: 10.1038/22118
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    Cited by:

    1. Toru Nakamura & Toru Takumi & Atsuko Takano & Naoko Aoyagi & Kazuhiro Yoshiuchi & Zbigniew R Struzik & Yoshiharu Yamamoto, 2008. "Of Mice and Men — Universality and Breakdown of Behavioral Organization," PLOS ONE, Public Library of Science, vol. 3(4), pages 1-8, April.
    2. Toru Nakamura & Toru Takumi & Atsuko Takano & Fumiyuki Hatanaka & Yoshiharu Yamamoto, 2013. "Characterization and Modeling of Intermittent Locomotor Dynamics in Clock Gene-Deficient Mice," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-8, March.
    3. Valerie L Harbour & Yuval Weigl & Barry Robinson & Shimon Amir, 2013. "Comprehensive Mapping of Regional Expression of the Clock Protein PERIOD2 in Rat Forebrain across the 24-h Day," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-14, October.

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